Neuronal cells have several unique characteristics which dramatically influence their metabolism: they are exquisitely sensitive to alterations in their environment; most of the cell volume is in axons and dendrites; synaptic transmission influences all aspects of their function. Studies on the control mechanisms of neuronal mRNA metabolism and function have been hampered by the brain's extraordinary complexity. We therefore propose a developmental study of the regulation of messenger RNA and protein synthesis in a discreet area, the rat cerebellum. The advantages of such a study are: the cerebellum is relatively homogeneous; it is composed of greater than 90% neurons, most being granule cells, at all developmental stages; it is well characterized morphologically; its development is mostly postnatal and takes place in well-defined stages. Hence, it will be possible to correlate transcriptional and translational changes with specific developmental events. In preliminary experiments, we have used two dimensional gel electrophoresis to characterize the abundant proteins synthesized both in vivo and in in vitro cell free protein synthesing systems in the 6-day and 90-day cerebellum. We find a relative decrease in the synthesis of the beta tubulin subunit with age as well as fluctuations in the steady state levels of many other proteins. We shall use these techniques to contrast the specific protein and mRNA levels at certain developmental stages, to compare transcriptional and translational control in neuronal metabolism and to investigate the specific roles of the free and membrane-bound polysomes in protein synthesis. We shall concurrently use specific affinity and antibody precipitation techniques to study the regulation of synthesis of several classes of neuronal proteins such as abundant structural proteins (e.g., the tubulins); regulatory proteins (e.g., the cAMP binding proteins); and synaptosomal proteins (e.g., A105, A78, A45). These experiments will lead to the use of genetic engineering techniques to study further aspects of neuronal mRNA metabolism during normal and abnormal development.